New Rodent Population Models May Inform Human Health Risk Assessment and Identification of Genetic Susceptibility to Environmental Exposures.
New Rodent Population Models May Inform Human Health Risk Assessment and Identification of Genetic Susceptibility to Environmental Exposures.
复制标题
新的啮齿动物种群模型可能会为人类健康风险评估和确定对环境暴露的遗传敏感性的识别。
DOI：
10.1289/ehp1274
复制
发表时间：
2017-08-15
影响因子：
10.4
通讯作者：
McAllister KA
中科院分区：
文献类型：
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作者：
Harrill AH;McAllister KA
本文介绍了环境卫生科学家新兴的人口为基础的啮齿动物资源。小鼠参考群体为模拟人类疾病中的环境暴露和基因-环境相互作用提供了机会，并为人类健康风险评估提供了信息。本次审查将描述几个小鼠种群的毒性评估，包括旧的模型，如小鼠多样性小组（MDP），和较新的模型，包括协作杂交（CC）和多样性远交（DO）模型。本次审查将概述的MDP，CC和DO小鼠模型的功能，并将讨论已发表的案例研究调查使用这些小鼠种群资源的风险评估范例的每一步。这些独特的资源有可能成为强有力的工具，用于生成与人类疾病中基因-环境相互作用相关的假设，进行受控暴露研究以了解人类对环境暴露的敏感性或抗性的差异反应，并确定影响对毒性和疾病状态敏感性的基因变异。这些新的资源提供了重大进展，包括遗传敏感的个人，可能会告知敏感亚群的毒性风险的经典毒性测试范例。体内和体外补充资源都提供了平台，通过提供生物变异性的群体水平数据来减少不确定性。https://doi.org/10.1289/EHP1274
This paper provides an introduction for environmental health scientists to emerging population-based rodent resources. Mouse reference populations provide an opportunity to model environmental exposures and gene–environment interactions in human disease and to inform human health risk assessment. This review will describe several mouse populations for toxicity assessment, including older models such as the Mouse Diversity Panel (MDP), and newer models that include the Collaborative Cross (CC) and Diversity Outbred (DO) models. This review will outline the features of the MDP, CC, and DO mouse models and will discuss published case studies investigating the use of these mouse population resources in each step of the risk assessment paradigm. These unique resources have the potential to be powerful tools for generating hypotheses related to gene–environment interplay in human disease, performing controlled exposure studies to understand the differential responses in humans for susceptibility or resistance to environmental exposures, and identifying gene variants that influence sensitivity to toxicity and disease states. These new resources offer substantial advances to classical toxicity testing paradigms by including genetically sensitive individuals that may inform toxicity risks for sensitive subpopulations. Both in vivo and complementary in vitro resources provide platforms with which to reduce uncertainty by providing population-level data around biological variability. https://doi.org/10.1289/EHP1274